Benzodiazepines are thought to have four general types of clinical effects: anxiolytic, muscle relaxant, hypnotic and anticonvulsant. One outgrowth of our previous work with benzodiazepine antagonists and sleep has been an interest in the role of GABA in the proconvulsant and anticonvulsant effects of drugs which bind to the benzodiazepine receptor. A current hypothesis suggested that drugs whose affinity to the receptor is decreased by GABA will be convulsants, while drugs whose affinity is enhanced will be anticonvulsants. This theory would predict that 3-carboethoxy-beta-carboline (beta-CCE), would have minimal or no proconvulsant properties, whereas the methoxy derivative (beta-CCM) would be a convulsant. Our laboratory demonstrated that when EEG criteria are used, beta-CCE will indeed induce electroencephalographic responses in rats, and our concurrent biochemical work indicated that the difference in effect can be explained by a faster rate of metabolism of beta-CCE. Similarly, biochemical studies in monkeys showed that the difference in relative resistance of rats to these seizures, and the relative ease of inducing seizures in squirrel monkeys, could be largely explained by rate of metabolism. These studies emphasize the importance of pharmacokinetic considerations as well as the role of GABA in drugs affecting seizure activity.